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Stroke ischemia reperfusion

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https://www.readbyqxmd.com/read/27929536/hyperhomocysteinemia-causes-er-stress-and-impaired-autophagy-that-is-reversed-by-vitamin-b-supplementation
#1
Madhulika Tripathi, Cheng Wu Zhang, Brijesh Kumar Singh, Rohit Anthony Sinha, Kyaw Thu Moe, Deidre Anne DeSilva, Paul Michael Yen
Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27928652/enhanced-proteostasis-in-post-ischemic-stroke-mouse-brains-by-ubiquilin-1-promotes-functional-recovery
#2
Yanying Liu, Fangfang Qiao, Hongmin Wang
Stroke is pathologically associated with oxidative stress, protein damage, and neuronal loss. We previously reported that overexpression of a ubiquitin-like protein, ubiquilin-1 (Ubqln), protects neurons against ischemia-caused brain injury, while knockout of the gene exacerbates cerebral ischemia-caused neuronal damage and delays functional recovery. Although these observations indicate that Ubqln is a potential therapeutic target, transgenic manipulation-caused overexpression of Ubqln occurs before the event of ischemic stroke, and it remains unknown whether delayed Ubqln overexpression in post-ischemic brains within a clinically relevant time frame is still beneficial...
December 7, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27927188/investigating-potentially-salvageable-penumbra-tissue-in-an-in-vivo-model-of-transient-ischemic-stroke-using-sodium-diffusion-and-perfusion-magnetic-resonance-imaging
#3
Friedrich Wetterling, Eva Chatzikonstantinou, Laurent Tritschler, Stephen Meairs, Marc Fatar, Lothar R Schad, Saema Ansar
BACKGROUND: Diffusion magnetic resonance imaging (MRI) is the current-state-of-the-art technique to clinically investigate acute (0-24 h) ischemic stroke tissue. However, reduced apparent diffusion coefficient (ADC)-considered a marker of tissue damage-was observed to reverse spontaneously during the subacute stroke phase (24-72 h) which means that low ADC cannot be used to reflect the damaged tissue after 24 h in experimental and clinical studies. One reason for the change in ADC is that ADC values drop with cytotoxic edema (acute phase) and rise when vasogenic edema begins (subacute phase)...
December 7, 2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27924073/diagnostic-performance-of-peroxiredoxin-1-to-determine-time-of-onset-of-acute-cerebral-infarction
#4
Sébastien Richard, Vanessa Lapierre, Nicolas Girerd, Mathieu Bonnerot, Pierre R Burkhard, Linnéa Lagerstedt, Serge Bracard, Marc Debouverie, Natacha Turck, Jean-Charles Sanchez
Accurately determining time-of-onset of cerebral infarction is important to clearly identify patients who could benefit from reperfusion therapies. We assessed the kinetics of peroxiredoxin 1 (PRDX1), a protein involved in oxidative stress during the acute phase of ischemia, and its ability to determine stroke onset in a population of patients with known onset of less than 24 hours and in a control group. Median PRDX1 levels were significantly higher in stroke patients compared to controls. PRDX1 levels were also higher from blood samples withdrawn before vs...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909732/early-vegf-inhibition-attenuates-blood-brain-barrier-disruption-in-ischemic-rat-brains-by-regulating-the-expression-of-mmps
#5
Hai-Tao Zhang, Ping Zhang, Yi Gao, Chen-Long Li, Hong-Jun Wang, Ling-Chao Chen, Yan Feng, Rui-Yan Li, Yong-Li Li, Chuan-Lu Jiang
Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion...
November 29, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27909230/the-protective-role-of-sex-hormones-in-females-and-exercise-prehabilitation-in-males-on-sternotomy-induced-cranial-hypoperfusion-in-aortic-banded-mini-swine
#6
T Dylan Olver, Jessica A Hiemstra, Jenna C Edwards, Brian S Ferguson, Harold Laughlin, Craig A Emter
During cardiac surgery, specifically sternotomy, cranial hypoperfusion is linked to cerebral ischemia, increased risk of perioperative watershed stroke and other neurocognitive complications. The purpose of this study was to retrospectively examine the effect of sex hormones in females and exercise prehabilitation in males on median sternotomy-induced changes in cranial perfusion in a large animal model of heart failure. Cranial blood flow (CBF) before, 10- and 60 min post-sternotomy was analyzed in eight groups of Yucatan mini-swine: female-control, aortic-banded, ovariectomized, and ovariectomized+aortic-banded; male-control, aortic-banded, aortic-banded+continuous exercise trained, and aortic-banded+interval exercise trained...
December 1, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27902774/intravenous-treatment-with-a-long-chain-omega-3-lipid-emulsion-provides-neuroprotection-in-a-murine-model-of-ischemic-stroke-a-pilot-study
#7
Dirk Berressem, Konrad Koch, Nicole Franke, Jochen Klein, Gunter P Eckert
Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)) are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV) that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml) and α-tocopherol (0.2 mg/ml) in a transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO...
2016: PloS One
https://www.readbyqxmd.com/read/27900597/l-pgds-mediates-vagus-nerve-stimulation-induced-neuroprotection-in-a-rat-model-of-ischemic-stroke-by-suppressing-the-apoptotic-response
#8
Lina Zhang, Jingxi Ma, Xinhao Jin, Gongwei Jia, Ying Jiang, Changqing Li
The role of lipocalin prostaglandin D2 synthase (L-PGDS) in brain ischemia has not been fully clarified to date. Vagus nerve stimulation (VNS) protects against cerebral ischemia/reperfusion (I/R) injury, but the mechanisms involved need further exploration. This study investigated the role of L-PGDS in cerebral I/R and whether this process was involved in the mechanism of VNS-mediated neuroprotection. Male Sprague-Dawley rats were pretreated with a lentiviral vector (LV) through intracerebroventricular injection, followed by middle cerebral artery occlusion (MCAO) and VNS treatment...
November 29, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27898011/update-on-inflammatory-biomarkers-and-treatments-in-ischemic-stroke
#9
REVIEW
Aldo Bonaventura, Luca Liberale, Alessandra Vecchié, Matteo Casula, Federico Carbone, Franco Dallegri, Fabrizio Montecucco
After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27896650/neuroprotection-by-chlorpromazine-and-promethazine-in-severe-transient-and-permanent-ischemic-stroke
#10
Xiaokun Geng, Fengwu Li, James Yip, Changya Peng, Omar Elmadhoun, Jiamei Shen, Xunming Ji, Yuchuan Ding
Previous studies have demonstrated depressive or hibernation-like roles of phenothiazine neuroleptics [combined chlorpromazine and promethazine (C + P)] in brain activity. This ischemic stroke study aimed to establish neuroprotection by reducing oxidative stress and improving brain metabolism with post-ischemic C + P administration. Sprague-Dawley rats were subjected to transient (2 or 4 h) middle cerebral artery occlusion (MCAO) followed by 6 or 24 h reperfusion, or permanent (28 h) MCAO without reperfusion...
November 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27894149/2-3-5-4-tetrahydroxystilbene-2-o-%C3%AE-d-glucoside-attenuates-ischemia-reperfusion-induced-brain-injury-in-rats-by-promoting-angiogenesis
#11
Ying Mu, Zhaohui Xu, Xuanxuan Zhou, Huinan Zhang, Qian Yang, Yunlong Zhang, Yanhua Xie, Juan Kang, Feng Li, Siwang Wang
Cerebral ischemia can cause brain infarcts, which are difficult to recover due to poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside is a natural polyphenol, has antioxidant and anti-inflammatory activity, and can protect from ischemic neuronal injury. However, little is known about the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside on brain microcirculation after stroke. This study aimed at investigating the influence of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside on brain lesions and angiogenesis after stroke...
November 28, 2016: Planta Medica
https://www.readbyqxmd.com/read/27882949/sumo-specific-protease-1-protects-neurons-from-apoptotic-death-during-transient-brain-ischemia-reperfusion
#12
Huijun Zhang, Yan Wang, Aoxue Zhu, Dehua Huang, Shining Deng, Jinke Cheng, Michael X Zhu, Yong Li
SUMO-specific protease 1 (SENP1) deconjugates SUMO from modified proteins. Although post-ischemic activation of SUMO conjugation was suggested to be neuroprotective against ischemia/reperfusion (I/R) injury, the function of SENP1 in this process remained unclear. Here we show that transient middle cerebral artery occlusion in mice followed by 6, 12 and 24 h reperfusion significantly enhanced SENP1 levels in the affected brain area, independent of transcription. Consistent with the increase in SENP1, the levels of SUMO1-conjugated proteins were decreased by I/R in cortical neurons of control littermate mice, but unchanged in that of animals with conditional ablation of SENP1 gene from adult principal neurons, the SENP1(flox/flox):CamKIIα-Cre (SENP1 cKO) mice...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27879370/validation-of-mri-determination-on-pet-measurements-in-ischemic-stroke
#13
Wolf-Dieter Heiss, Olivier Zaro Weber
The concept of the ischemic penumbra was formulated based on animal experiments showing functional impairment and electrophysiological disturbances with decreasing flow to the brain below defined values (the threshold for function) and irreversible tissue damage with blood supply further decreased (the threshold for infarction). The perfusion range between these thresholds was termed "penumbra", and restitution of flow above the functional threshold was able to reverse the deficits without permanent damage...
November 22, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27869849/optical-coherence-tomography-imaging-of-capillary-reperfusion-after-ischemic-stroke
#14
Jonghwan Lee, Yasemin Gursoy-Ozdemir, Buyin Fu, David A Boas, Turgay Dalkara
Although progress has been made for recanalization therapies after ischemic stroke, post-treatment imaging studies show that tissue reperfusion cannot be attained despite satisfactory recanalization in a significant percentage of patients. Hence, investigation of microcirculatory changes in both surface and deep cortical levels after ischemia reperfusion is important for understanding the post-stroke blood flow dynamics. In this study, we applied optical coherence tomography (OCT) imaging of cerebral blood flow for the quantification of the microcirculatory changes...
November 20, 2016: Applied Optics
https://www.readbyqxmd.com/read/27867482/normobaric-oxygen-treatment-in-acute-ischemic-stroke-a-clinical-perspective
#15
REVIEW
Shu-Hai Shi, Zhi-Feng Qi, Yu-Min Luo, Xun-Ming Ji, Ke Jian Liu
Acute ischemic stroke is a common and serious neurological disease. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve outcomes after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBO), an easily applicable and non-invasive method, shows protective effects on acute ischemic stroke animals and patients in pilot studies. However, many critical scientific questions are still unclear, such as the therapeutic time window of NBO, the long-term effects and the benefits of NBO in large clinic trials...
July 2016: Medical Gas Research
https://www.readbyqxmd.com/read/27867480/xenon-protects-left-ventricular-diastolic-function-during-acute-ischemia-less-than-ischemic-preconditioning
#16
Jan-H Baumert, Anna B Roehl, Sandra Funcke, Marc Hein
Anesthetics modify regional left ventricular (LV) dysfunction following ischemia/reperfusion but their effects on global function in this setting are less clear. Aim of this study was to test the hypothesis that xenon would limit global LV dysfunction as caused by acute anterior wall ischemia, comparable to ischemic preconditioning. In an open-chest model under thiopental anesthesia, 30 pigs underwent 60-minute left anterior descending coronary artery occlusion, followed by 120 minutes of reperfusion. A xenon group (constant inhalation from previous to ischemia through end of reperfusion) was compared to control and ischemic preconditioning...
July 2016: Medical Gas Research
https://www.readbyqxmd.com/read/27864466/thiamet-g-mediates-neuroprotection-in-experimental-stroke-by-modulating-microglia-macrophage-polarization-and-inhibiting-nf-%C3%AE%C2%BAb-p65-signaling
#17
Yating He, Xiaofeng Ma, Daojing Li, Junwei Hao
Inflammatory responses are accountable for secondary injury induced by acute ischemic stroke (AIS). Previous studies indicated that O-GlcNAc modification (O-GlcNAcylation) is involved in the pathology of AIS, and increase of O-GlcNAcylation by glucosamine attenuated the brain damage after ischemia/reperfusion. Inhibition of β-N-acetylglucosaminidase (OGA) with thiamet G (TMG) is an alternative option for accumulating O-GlcNAcylated proteins. In this study, we investigate the neuroprotective effect of TMG in a mouse model of experimental stroke...
November 18, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27861531/macrophage-derived-angiopoietin-like-protein-2-exacerbates-brain-damage-by-accelerating-acute-inflammation-after-ischemia-reperfusion
#18
Toshihiro Amadatsu, Jun Morinaga, Takayuki Kawano, Kazutoyo Terada, Tsuyoshi Kadomatsu, Keishi Miyata, Motoyoshi Endo, Daiki Kasamo, Jun-Ichi Kuratsu, Yuichi Oike
Ischemic stroke is a leading cause of death and disability worldwide. Several reports suggest that acute inflammation after ischemia-reperfusion exacerbates brain damage; however, molecular mechanisms underlying this effect remain unclear. Here, we report that MAC-3-positive immune cells, including infiltrating bone marrow-derived macrophages and activated microglia, express abundant angiopoietin-like protein (ANGPTL) 2 in ischemic mouse brain in a transient middle cerebral artery occlusion (MCAO) model. Both neurological deficits and infarct volume decreased in transient MCAO model mice established in Angptl2 knockout (KO) relative to wild-type mice...
2016: PloS One
https://www.readbyqxmd.com/read/27858286/hypoxic-preconditioning-augments-the-therapeutic-efficacy-of-bone-marrow-stromal-cells-in-a-rat-ischemic-stroke-model
#19
Jin Chen, Yuanyuan Yang, Lihua Shen, Wensen Ding, Xiang Chen, Erbing Wu, Kefu Cai, Guohua Wang
Transplantation of bone marrow stromal cells (BMSCs) is a promising therapy for ischemic stroke, but the poor oxygen environment in brain lesions limits the efficacy of cell-based therapies. Here, we tested whether hypoxic preconditioning (HP) could augment the efficacy of BMSC transplantation in a rat ischemic stroke model and investigated the underlying mechanism of the effect of HP. In vitro, BMSCs were divided into five passage (P0, P1, P2, P3, and P4) groups, and HP was applied to the groups by incubating the cells with 1% oxygen for 0, 4, 8, 12, and 24 h, respectively...
November 18, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27856349/reparative-effects-of-interleukin-1-receptor-antagonist-in-young-and-aged-co-morbid-rodents-after-cerebral-ischemia
#20
Jesus M Pradillo, Katie N Murray, Graham A Coutts, Ana Moraga, Fernando Oroz-Gonjar, Herve Boutin, Maria A Moro, Ignacio Lizasoain, Nancy J Rothwell, Stuart M Allan
Neuroprotective strategies for ischemic stroke have failed to translate from bench to bedside, possibly due to the lack of consideration of key clinical co-morbidities. Stroke and co-morbidities are associated with raised levels of the pro-inflammatory cytokine interleukin-1 (IL-1). Inhibition of IL-1 by the administration of interleukin-1 receptor antagonist (IL-1Ra) has shown to be neuroprotective after experimental cerebral ischemia. Stroke can also trigger a robust neuroreparative response following injury, yet many of these new born neurons fail to survive or integrate into pre-existing circuits...
November 14, 2016: Brain, Behavior, and Immunity
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